Because of concern that immune globulins (IG) containing HCV RNA may transmit hepatitis C, the infectivity of an IG prepared from a plasma pool derived solely from anti-c100-3 reactive donations was determined in a chimpanzee. The chimpanzee is the only known animal model for evaluation of HCV infection. This IG preparation, designated as HCIG, was a 5.2% protein solution, contained 250 PCR units/g IgG, and had an anti-HCV titer of 1:1024 when assayed by multiantigen EIA kit (Ortho). The HCIG was administered intravenously to a chimpanzee at a dosage of 500 mg IgG/kg bw per day for two consecutive days (total dose, 1 g/kg, equivalent to a rather large human dosage). The chimpanzee has been bled weekly and liver biopsied triweekly. Thus far, 3 months after infusion, alanine aminotransferase (ALT) levels remain in the normal range and HCV RNA has not been detected. The follow-up period for infectious markers (i.e., ALT and HCV RNA) will be 12 months; HCIG would be considered noninfectious if both parameters remain negative for that period and the chimpanzee is subsequently shown to be susceptible to HCV infection after challenge with a known infectious inoculum. The outcome of this study is of paramount importance in defining the infectivity of IG (and perhaps of other plasma derivatives) that contain HCV RNA, and may serve as a basis for further studies on possible protective antibodies in HCIG.